POS0178 DISEASE ACTIVITY GUIDED TAPERING OF RITUXIMAB IN CLINICAL PRACTICE: A RETROSPECTIVE COHORT STUDY OF RHEUMATOID ARTHRITIS PATIENTS
Authors: M. Wientjes, J. Van Huissteden, L. M. Verhoef, A. Den Broeder
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> The REDO trial (REtreatment with Rituximab in RhEumatoid arthritis: Disease Outcome after Dose Optimisation) showed that ultra-low-dose (500mg or 200mg) rituximab (RTX) was similarly effective to 1000mg in the majority of rheumatoid arthritis (RA) patients. [1] These results led to the implementation of a disease activity guided dose optimization (DAGDO) protocol for RTX at the Sint Maartenskliniek since January 2019. This protocol includes stepwise tapering of RTX (after the initial dose of 1000mg) towards 500mg, 200mg and full withdrawal if DAS28-CRP &lt; 2.4 (or 2.9 in patients with disease duration &gt;3 years). <h3>Objectives</h3> We aimed to validate the findings from the REDO study in clinical practice, by determining the effect of RTX tapering on disease activity and RTX dosage compared to standard low dose RTX treatment (≥1000mg every six months). <h3>Methods</h3> A retrospective cohort was conducted of patients who 1) used RTX between April 2012 and February 2022, 2) had a clinical diagnosis of rheumatoid arthritis (according to either 1987 or 2010 ACR criteria, and/or by clinical diagnosis from the treating rheumatologist, 3) were eligible for dose reduction (i.e. reached a DAS28-CRP score of 3.5 or lower for at least 6 consecutive months during RTX use), and 4) had at least two DAS28-CRP measurements during follow-up. We identified three treatment periods for which we compared the mean disease activity scores: (i) full dose RTX continuation period, (ii) RTX DAGDO period, and (iii) stable RTX dose (and interval) after DAGDO (at least 12 months after the last tapering attempt). Primary outcome was the difference in mean DAS28-CRP between the three treatment periods. This was analysed using a linear mixed-model with a random intercept, including age, disease duration, concomitant csDMARD use (all at moment of DAS28 measurement), seropositivity for ACPA and/or rheumatoid factor and sex as potential confounders. The mean percentage of the rituximab Daily Defined Dose (%DDD) per treatment period was calculated as secondary outcome, with 1000mg/6months as 100% reference. <h3>Results</h3> A total of 387 patients were included in the cohort, with a mean of 9.2 DAS28-CRP measurements (SD: 6.0) available per patient. Median follow-up time was 46 months (IQR: 25-78). 299 patients attempted tapering during follow-up and entered period 2 at least once, of whom 226 also entered period 3. The mean DAS28-CRP was 2.37 (95% CI: 2.29, 2.44) for period 1, 2.32 (95% CI: 2.24, 2.40) for period 2, and 2.27 (95% CI: 2.18, 2.36) for period 3, the latter significantly lower compared to period 1 (p=0.022). The mean percentage of the DDD for the three time periods was 111% for the continuation period; 64% in the DAGDO period and 71% in the stable RTX dosage period. <h3>Conclusion</h3> This relatively large retrospective cohort study shows that DAGDO of RTX is effective for rheumatoid arthritis patients doing well on full dose rituximab, and leads to relevant dose reduction. The lower mean disease activity scores in period 3 may be affected by survival bias, as solely patients using RTX successfully for a longer time reach period 3. However most patients that entered period 2 also entered period 3, and mean disease activity in period 2 was not increased compared to period 1. Wide implementation of tapering protocols for RTX in RA patients should be contemplated. <h3>Reference</h3> [1]LM Verhoef et al. Ultralow dose of rituximab for continued treatment of rheumatoid arthritis (REDO study): a randomized controlled non-inferiority trial. Lancet Rheumatol 2019;1: 145–53. <h3>Acknowledgements</h3> I have no acknowledgements to declare. <h3>Disclosure of Interests</h3> Maike Wientjes: None declared, Jordy van Huissteden: None declared, L.M. Verhoef: None declared, Alfons den Broeder Grant/research support from: Grants to the institution from Abbvie, Gilead, Pfizer, Novartis, Lilly, Galapagos, Sanofi.